1. Field of the Invention
The present invention relates to a method of administering an androgen such as dehydroepiandrosterone (DHEA) for at least two months to a human female, usually one with decreased ovarian function. The administration of DHEA for at least two months has varied and widespread effects such as improving the number and quality of eggs a woman produces along with improving the number and quality of embryos. The administration of DHEA also improves spontaneous pregnancy rates, the in vitro fertilization (IVF) pregnancy rates, cumulative pregnancy rates, and time to conception. Moreover, the administration of DHEA for at least two months reduces miscarriage rates by most likely, at least partially, reducing aneuploidy rates. Further, the administration of DHEA also increases the male to female birth ratio. The method, results, and benefits of DHEA administration for at least two months to a human female are disclosed herein in the description and following examples.
2. Description of the Related Art
The application of assisted reproductive technology has revolutionized the treatment of all forms of infertility. The most common assisted reproductive technology is in vitro fertilization (IVF), in which a woman's eggs are harvested and fertilized with a man's sperm in a laboratory. Embryos grown from the sperm and eggs are then chosen to be transferred into the woman's uterus. Assisted reproductive technology in women depends on ovarian stimulation and concurrent multiple oocyte development, induced by exogenous gonadotropins.
Infertile women are often treated with gonadotropin treatments such as gonadotropin-releasing hormone (GnRH) flare protocols. Estrogen pre-treatment with concomitant growth hormone (GH) treatment is sometimes used in an effort to try and amplify intra-ovarian insulin-like growth factor-I (IGF-I) paracrine effect, which is expressed by granulosa cells and enhances gonadotropin action. However, the clinical utility of combined GH/ovarian stimulation is limited and responses are not dramatic.
Dehydroepiandrosterone (DHEA) is secreted by the adrenal cortex, central nervous system and the ovarian theca cells and is converted in peripheral tissue to more active forms of androgen or estrogen. DHEA secretion during childhood is minimal but it increases at adrenarche and peaks around age 25, the age of maximum fertility, only to reach a nadir after age 60. There is evidence to support use of exogenous DHEA to increase ovulation stimulation in older women who respond poorly to gonadotropin treatments. Older women with diminished ovarian function have decreased egg production and the eggs that are produced usually are of a poor quality. Further, women with diminished ovarian function tend to encounter difficulty becoming pregnant with or without IVF and experience long time periods to conception.
Even when these women do achieve a pregnancy, the rate of a possible miscarriage increases. A large majority of approximately 80 percent of spontaneous pregnancy loss is the consequence of chromosomal abnormalities. As women get older and their ovarian function progressively declines, miscarriage rates rise because of increasing aneuploidy.
Women with diminished ovarian function have largely been considered to be untreatable.